DESCRIPTION: The disease prognosis for HIV positive individuals is markedly improved if viral loads are kept at a minimum. Some non-progressors appear to have an innate ability to control virus expression in the absence of antiviral therapies and it is generally assumed that this control of viremia is largely dictated by the humoral and/or cellular immune response to the virus. However, both non-progressors and rapid progressors exhibit substantial immune responses to HIV, with humoral antibody responses particularly directed at the major neutralization target, the viral envelope. Studies of the humoral antibody response associated with FIV infection has revealed the presence of antibodies to the primary binding receptor, CD134, in a high percentage of infected cats. Furthermore, these anti-CD134 antibodies blocked FIV infection ex vivo and their presence correlated with low/slow disease progression in vivo. Reactivity with CD134 occurs at a cryptic epitope that is only exposed when virus binds, thus avoiding potential autoimmune issues. The purpose of the present studies is to pursue characterization of the homologous anti-receptor antibodies against the HIV primary binding receptor, CD4 that we have identified in screening the sera of approximately 300 HIV-infected patients. We wish to determine whether there is a relationship between rate/extent of disease progression and generation of anti-CD4 antibody responses; and 2) whether a subset of anti-CD4 antibodies interfere with HIV infection. To this end, we propose the following Aims: 1). Use Immunoaffinity to purify anti-CD4 antibodies from patient serum and assess the influence of those antibodies on virus uptake into target cells; and 2) Continue screening of additional patient serum to assess anti-CD4,anti-SU, and anti-Gag humoral antibody responses as a function of rate/extent of disease progression, as measured by relative CD4+ and CD8+ T cell levels and viral load. The findings will increase our understanding of the nature of the antiviral response as it relates to protection and thus aid in development of more efficacious vaccine strategies.